On June 22, 2017, Seattle Genetics confirmed it discontinued the phase III CASCADE clinical trial of vadastuximab talirine (SGN-CD33A) in front-line older acute myeloid leukemia (AML) patients. Patient enrollment and treatment in all of its vadastuximab talirine clinical trials are suspended, including the ongoing phase I/II clinical trial in front-line high-risk myelodysplastic syndrome.
The phase III CASCADE clinical trial is a randomized, double-blind, placebo-controlled study evaluating vadastuximab talirine in combination with the hypomethylating agents azacitidine or decitabine compared with hypomethylating agents alone in older patients with newly diagnosed AML. Vadastuximab talirine is a novel investigational antibody-drug conjugate targeted to CD33 utilizing Seattle Genetics’ proprietary antibody-drug conjugate technology. CD33 is expressed on most AML and myelodysplastic syndrome blast cells.
The company took this action following consultation with the independent data monitoring committee and after reviewing unblinded data on June 16, 2017. The data indicated a higher rate of deaths, including fatal infections, in the vadastuximab talirine–containing arm vs the control arm of the trial. Based on the available data, the safety concerns in this trial do not appear related to hepatotoxicity.
The company confirmed it will closely review the data and consult with the U.S. Food and Drug Administration (FDA) to determine future plans for the vadastuximab talirine development program.
“This is a disappointing and unexpected result for the CASCADE trial. Patient safety is our highest priority, and we will closely review the data and evaluate next steps. AML is a devastating disease with a poor prognosis in most patients, and there is a great need for therapeutics against this disease. We thank the patients, caregivers, and investigators for their support of this trial,” said Clay Siegall, PhD, President and Chief Executive Officer at Seattle Genetics.
“We are enthusiastic about the many opportunities across our broad pipeline, including brentuximab vedotin (Adcetris), enfortumab vedotin (ASG-22ME), and SGN-LIV1A. Notably, we are looking forward to reporting data from our ADCETRIS phase III ECHELON-1 trial in front-line Hodgkin lymphoma, and we are on track to advance enfortumab vedotin into a pivotal trial in metastatic urothelial cancer in the second half of 2017 under our collaboration with Astellas,” Dr. Siegall concluded. ■